Bleeding profile in users of an etonogestrel sub-dermal implant: effects of anthropometric variables. An observational uncontrolled preliminary study in Italian population.

PURPOSE: The purpose of this study is to evaluate the menstrual profile in users of the etonogestrel (ENG)-releasing implant (Nexplanon®) and the possible correlation with anthropometric variables. METHODS: Ninety-two healthy women, desiring long-term contraception with the ENG implant were enrolled in a prospective observational study. Anthropometric variables were measured at baseline and after 3, 6, 9, and 12 months. Patients recorded daily the occurrence of any bleeding or spotting. The bleeding/spotting pattern was evaluated over consecutive 90-day intervals ("Reference Periods" - RPs). Patients who showed a favourable bleeding profile (amenorrhoea, infrequent, or normal bleeding) for 50% or more of the RPs were assigned to group A, while patients with a favourable bleeding profile for less than 50% of the RPs were assigned to group B. RESULTS: Sixty-eight women (79%) were assigned to group A; 18 (21%) to group B. Group B had a lower baseline body mass index (BMI) than group A (24.84 ± 4.95 kg/m(2) versus 20.75 ± 4.41 kg/m(2); p < 0.005). CONCLUSIONS: The ENG sub-dermal implant is a well-tolerated contraceptive method, with a high proportion of women experiencing a favourable bleeding profile. The lower basal BMI in Group B in comparison with Group A may account for the higher percentage of irregular bleeding.

Effects of estradiol valerate and dienogest on quality of life and sexual function according to age.

This is an observational study on 102 women aged 25-45 years to evaluate if the E2V/DNG pill has any impact on quality of life (QoL) and sexual function (FSF). Thirty-nine women were younger than 35 years (group A), and 63 women were 35 years old or older (group B). At baseline and after 6 months, patients received the Italian validated version of the Short Form-36 questionnaire and the Italian validated version of the Female Sexual Function Index questionnaire. Group A showed an overall higher perception in all QoL scores at baseline and after 6-months (p < 0.05). E2V/DNG treatment did not exert any significant effect on QoL perception in group A apart from an increase in the GH domain (general health). In group B we observed a significant improvement both in GH and in VT (vitality) scores. We found a significant reduction in "lubrication" after 6 months both in group A and B (p < 0.01) and a significant improvement in "satisfaction" and "pain" scores in group A and in "desire", "satisfaction" and "total" score in group B (p < 0.01). The E2V/DNG pill is associated with a significant improvement of GH and VT and with an improvement in FSF with no difference between age groups.

Impact of an implantable steroid contraceptive (etonogestrel-releasing implant) on quality of life and sexual function: a preliminary study.

The aim of the study was to determine the impact of etonogestrel (ENG)-implant used for contraceptive purpose on Quality of life (QoL) and on sexual function (FSF) of healthy Italian women. The Female Sexual Function Index (FSFI) questionnaire and the Short Form-36 (SF-36) validated questionnaire were administered at baseline, 3 and 6 months after insertion of Nexplanon. The implant seems to have a positive impact on QoL after the first three months of therapy. Users showed an improved general health status and physical role status. The implant did not show negative effects on libido and on sexual function. In the first three months of treatment, users experienced a temporary reduction of vitality, mental health, social functioning and emotional role functioning, which seem to disappear after six months of therapy.

Effects of an oral contraceptive containing estradiol valerate and dienogest on circulating androgen levels and acne in young patients with PCOS: an observational preliminary study.

This study shows the effect of a 1 year treatment with an estradiol valerate/dienogest pill in 36 women suffering from polycystic ovaries and mild or moderate acne. At beginning of the study, 24 patients (66.7%) had grade 1-2 (mild) acne and 12 patients (33.3%) had grade 3 (moderate) acne. After 12 cycles of therapy, we found an improvement of acne in 19 (52.8%) patients and a worsening of acne in 3 (8.4%) patients. The percentage of patients recovered was statistically significant (p < 0.01). SHBG levels were significantly higher after 6 and 12 months of therapy (p < 0.001), while total testosterone levels were lower in all patients at 6 and 12 months although this trend did not reach statistical significance. In conclusion, the present study suggests that the E2V/DNG pill could exert a positive influence on acne and hyperandrogenism. Since this is an observational study on a very limited population number, additional randomized controlled studies on larger populations are needed also to determine the effects of this contraceptive over longer periods of use.

Successful pregnancy complicated by spontaneous, familial, recurrent ovarian hyperstimulation syndrome: report of two cases.

We here report two cases of spontaneous, familial, recurrent ovarian hyperstimulation syndrome ended in a successful pregnancy. First case was a 26-year-old woman, gravida 3 para 0 and two previous terminations of pregnancy due to spontaneous ovarian hyperstimulation syndrome (OHSS). During her pregnancy, patient was treated with IV fluid therapy, albumin and thromboembolic prophylaxis and required pleural and peritoneal drainage. She was referred to the hospital twice, at 8 and 28 weeks'. At 32 weeks due to worsening of clinical condition, decision was made for a caesarean section. A live, healthy preterm baby of 1950 g was delivered. Second case was a 27-year-old woman, gravida 2 para 0 with one previous termination of pregnancy due to spontaneous OHSS. During her pregnancy patient was treated with IV fluid therapy, albumin, and thromboembolic prophylaxis. She did not require any pleural or peritoneal drainage. She was referred to the hospital twice, at 8 and 30 weeks. At 37 weeks of gestation, due to worsening of clinical condition decision for a caesarean section was made. A live, healthy term baby of 2700 g was delivered. Our experience seems to confirm that management of spontaneous OHSS during pregnancy should be conservative and treatment tailored to severity of symptoms.

Short-term effects of an oral contraceptive containing oestradiol valerate and dienogest on bone metabolism and bone mineral density: an observational, preliminary study.

OBJECTIVES: To evaluate the effects of a combined oral contraceptive (COC) containing dienogest/oestradiol valerate (DNG/E2V) on bone mineral density (BMD) and on serum and urinary bone turnover markers in young, healthy, fertile women. METHODS: At baseline and after three and six months of intake of the aforementioned COC, serum and urinary calcium, osteocalcin, urinary pyridinoline (PYD), and deoxypyridinoline (D-PYD) of 30 women aged 21 to 34 years were measured. At baseline and after six months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry (DEXA). RESULTS: Urinary levels of PYD and D-PYD were significantly lower at three and six months in comparison with basal values (p < 0.05). Serum calcium levels showed an increasing trend, which reached statistical significance after six months in comparison with basal values while urinary levels of calcium did not vary significantly. Serum osteocalcin levels were somewhat, but not significantly, lower during pill use in comparison with basal values. After six months, spinal BMD values did not differ significantly from basal values. CONCLUSIONS: The DNG/E2V COC has no short-term adverse effect on bone turnover markers. No significant change in BMD was observed after six months of use of that pill.

Efficacy and safety of TVT-O and TVT-Secur in the treatment of female stress urinary incontinence: 1-year follow-up.

INTRODUCTION AND HYPOTHESIS: To reduce complications of transobturator tension-free vaginal tape, single-incision devices were introduced in the last years. We here report a comparison between the tension-free vaginal tape-obturator (TVT-O) and the TVT-Secur techniques in terms of efficacy and safety. METHODS: Eighty-four patients with stress urinary incontinence (SUI) were scheduled to undergo TVT-O or TVT-Secur. Duration of the procedure, subjective estimate of blood loss, intraoperative and postoperative complications, postoperative postvoidal residue (PVR), time to first voiding, and pain level were recorded. Urodynamic tests, PVR, Incontinence Questionnaire Short Form (ICIQ-SF), King's Health Questionnaire, and a urinary diary were performed before and 12 months after procedure. RESULTS: No differences in terms of cure rate were observed between the two groups (81.6% vs. 83.8%). Complication rate in the TVT-Secur group was lower (8.1%) than in the TVT-O group (15.8%), but not significant. CONCLUSIONS: Both techniques seem to be effective and safe, with a low incidence of complications in both groups.

Effects of two low-dose combined oral contraceptives containing drospirenone on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study.

BACKGROUND: The effects of a 21-day combined oral contraceptive containing 30 mcg ethinyl estradiol plus 3 mg drospirenone with a 21-day preparation containing 20 mcg ethinyl estradiol plus 3 mg drospirenone on bone turnover and bone mineral density (BMD) in young fertile women were compared. METHODS: A randomized, controlled trial was conducted on healthy fertile women treated with 30 mcg ethinyl estradiol plus 3 mg drospirenone (Group A; n=21), 20 mcg ethinyl estradiol plus 3 mg drospirenone (Group B; n=23) and healthy controls (Group C; n=21). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin (BGP), urinary pyridinoline and deoxypyridinoline were measured. At baseline and after 12 months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry. RESULTS: In Groups A and B, urinary pyridinoline and deoxypyridinoline at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Groups A and B in urinary levels of pyridinoline and deoxypyridinoline, in calcium levels and in BGP levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values. CONCLUSION: Both combined oral contraceptives exert a similar positive influence on bone turnover in young postadolescent women.

Effects of estrogen-progestin therapy on serum levels of RANKL, osteoprotegerin, osteocalcin, leptin, and ghrelin in postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the effects of estrogen-progestin therapy on serum levels of receptor-activating nuclear factor kappabeta ligand (RANKL), osteoprotegerin, osteocalcin, leptin, and ghrelin in a cross-sectional study of 99 healthy postmenopausal women conducted at the Menopause Clinic of our department. DESIGN: In this cross-sectional, observational study, 99 participants were divided into two groups. Group A was composed of 77 postmenopausal women who had never received estrogen-progestin therapy, and group B was composed of 22 postmenopausal women who had received transdermal 17beta-estradiol at a dose of 50 microg/day in a continuous regimen for at least 24 months and nomegestrol at a dose of 5 mg/day for 12 days/month in a sequential regimen. All participants underwent blood sampling in the morning and quantitative ultrasound bone-densitometry measurement of the proximal phalanges of the dominant hand. RESULTS: T score and amplitude-dependent speed of sound were significantly higher in group B than in group A. No significant differences in RANKL, osteoprotegerin, and osteocalcin were observed between the two groups. Serum leptin levels were significantly lower in group B than in group A, whereas ghrelin was significantly higher in group B than in group A. CONCLUSIONS: The data gathered in this preliminary study indicate that estrogen-progestin therapy may protect against postmenopausal bone loss, but this protective effect does not seem to be exerted through action on the RANK-RANKL-osteoprotegerin system. Similarly, although several reports suggest that leptin and ghrelin are involved in bone metabolism, we could not detect any important correlation of these two hormones with bone metabolism or bone status in treated and untreated postmenopausal women. Because of the limited number of treated participants and the study design, the results of this preliminary study must be confirmed in larger, prospective, longitudinal studies.

Longitudinal evaluation of serum leptin and bone mineral density in early postmenopausal women.

OBJECTIVE: To evaluate total and site-specific bone mineral density (BMD) and serum leptin levels in postmenopausal women treated with a calcium supplement and in postmenopausal women receiving estrogen plus progestin therapy. DESIGN: Forty-four women were randomized to receive either calcium supplementation (group A, n = 22) or transdermal 17beta-estradiol at a dose of 50 mug/day in a continuous regimen and nomegestrol at a dose of 5 mg/day for 12 days per month in a sequential regimen (group B, n = 22). All women underwent dual-energy x-ray absorptiometry determination of BMD and blood sampling in the morning at the beginning of the study and after 12 months. Leptin was determined by radioimmunoassay in all samples. RESULTS: After 12 months, serum leptin levels were significantly higher in group A (control) in comparison with group B and baseline values, whereas both total and pelvic BMDs were significantly lower in group A in comparison with group B and baseline values. At baseline, a significant correlation was found between leptin levels, body mass index, and total-body BMD. After 12 months, leptin was still correlated to body mass index in both groups, but the association with BMD was lost. CONCLUSIONS: This study confirms previous evidence of a significant correlation between serum leptin and BMD in early postmenopausal women. Furthermore, this correlation is lost over time during the progression of the postmenopausal period, independently from the administration of estrogen-progestin therapy. Further studies and longer follow-up periods are needed to better understand theses issues.

Hormonal contraception and bone metabolism: a systematic review.

BACKGROUND: Although a large amount of studies in the literature evaluated the effects of hormonal contraception on bone, many questions remained still unclear, such as the effect of these therapies on fracture risk. STUDY DESIGN: We performed a systematic search of the published studies from January 1975 through January 2012 on the effects of hormonal contraceptives on bone metabolism. We analyzed the overall effect on bone mineral density (BMD) and on fracture risk of combined oral contraceptives (COCs), progestogen-only contraceptives, transdermal contraceptives and vaginal ring. RESULTS: COC therapy does not seem to exert any significant effect on BMD in the general population. In adolescents, the effects of COCs on BMD seem to be mainly determined by estrogen dose. The use of COCs in perimenopausal women seems to reduce bone demineralization and may significantly increase BMD even at a 20-mcg dose. Use of depot medroxyprogesterone acetate is associated with a decrease in BMD, although this decrease seems to be partially reversible after discontinuation. Data on other progestogen-only contraceptives, transdermal patch and vaginal ring are still limited, although it seems that these contraceptive methods do not exert any influence on BMD. CONCLUSIONS: Hormonal contraceptives do not seem to exert any significant effect on bone in the general population. However, other randomized controlled trials are needed to evaluate the effects on fracture risk since the data available are derived from studies having the effects on BMD as the primary end point, and BMD may not accurately reflect the real fracture risk.

Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study.

BACKGROUND: This study was conducted to compare the effects of the combined contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg of etonorgestrel daily with the effects of the contraceptive patch, a transdermal system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin on bone turnover and bone mineral density (BMD) in young fertile women. STUDY DESIGN: On the basis of a randomized, computer-generated list, 40 women desiring contraception were assigned to a 12-month treatment with a patch delivering a daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra, Janssen-Cilag, Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing, Organon, Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) levels were measured. At baseline and after 12 months, lumbar BMD was determined by dual-energy X-ray absorptiometry. RESULTS: In Groups A and B, urinary PYD and D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C values (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels and in osteocalcin levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values. CONCLUSION: Both contraceptive systems exert a similar positive influence on bone turnover in young postadolescent women.

Hysteroscopic treatment of atypical polypoid adenomyoma diagnosed incidentally in a young infertile woman.

OBJECTIVE: To describe the conservative treatment of an atypical polypoid adenomyoma (APA) in a young infertile patient using a modification of the technique previously reported for the conservative treatment of stage IA endometrial cancer. DESIGN: Case report. SETTING: Department of Gynaecology and Obstetrics and Pathophysiology of Human Reproduction of the University of Naples "Federico II." PATIENT(S): A 35-year-old woman diagnosed incidentally with an APA during routine investigation for primary infertility. INTERVENTION(S): Conservative resectoscopic treatment using a four-step technique in which each step is characterized by a pathological analysis: the removal of the APA (step 1), the removal of endometrium adjacent to the APA (step 2), the removal of the myometrium underlying the APA (step 3), and multiple random endometrial biopsies (step 4). MAIN OUTCOME MEASURE(S): Complete resection of the APA and ruling out of any malignancy. RESULT(S): The conservative surgery was effective as histological examination of all specimens confirmed an APA confined to the endometrium without any other premalignant or malignant lesion. Transvaginal ultrasound and office hysteroscopy with target biopsies at 1 and 6 months after surgery were negative for atypia and malignancy. CONCLUSION(S): Our technique under a close, intermittent postoperative surveillance might represent a good therapeutic option for those women with APA who wish to preserve their fertility as well as for those at high medical risk for hysterectomy.

Short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on climacteric-related symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled trial.

The present study aimed to evaluate the short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on acute climacteric-related symptoms in postmenopausal women in a double-blind, randomized, placebo-controlled trial performed at the menopause clinic of our department. Eighty healthy postmenopausal women were randomly assigned to two treatment groups - one receiving the combination (group A, n = 40), the other receiving calcium supplements (group B, n = 40) - for three cycles of 28 days. Climacteric-related symptoms were evaluated by the Kupperman index (KI) at baseline and after the three cycles of treatment. At baseline no significant difference was detected in KI between groups A and B; however, after three cycles of treatment, KI was significantly (p < 0.05) lower in group A compared with baseline and with group B. We conclude that the administration of a combination of isoflavones, lignans and C. racemosa already reduces acute climacteric symptoms in postmenopausal women after 3 months of treatment. This prompt effect is probably due to the different pharmacokinetic properties of isoflavones and lignans; isoflavones are absorbed faster than lignans, while lignans are removed later. The combination of these molecules can guarantee a better reduction of postmenopausal symptoms over a 24-h period.